How did tuberculosis cease to be a deadly killer in the West?
AMONG infectious diseases, tuberculosis
(TB) stands out as the principal exterminator of humans, with an estimated 8
million new cases and 2.9 million deaths
occuring worldwide annually. The situation is particularly alarming in developing countries, where 7 per cent of all
deaths, and 19 per cent of deaths of
adults between the ages of 19 and 59 are
due to TB.
However, the history Of TB in the
developed world is interesting. It was a
major killer 100-200 years ago, but the
number of fatalities fell thereafter.By
the time antibiotics first came on the
scene, they were no longer needed.
How did this happen? Among many
proferred explanations, one is that
improvements in hygiene standadards
reduced the frequency of transmision
of communicable diseases. Also
improved standards of living raised the
natural levels of resistance. Then there is
the possibility that if TB is transmitted
only by live individuals, an infection
that caused rapid death would not
spread far. Finally, an evolutionary
increase in the ability of humans to
resist infection has been
postulated.
A completely new theory for the past decline in
incidence of infectious TB
has now been advanced by
S M Blower of the
University of California
(San Francisco) and her
colleagues. This theory is
based on the analysis of a
mathematical model that
attempts to mimic the rise
and spread of a TB epidemic (Nature Medicine,
1, (8): 815-821).
Two approaches have
been explored. The simpler one considers three groups of individuals: those
susceptible to infection; those latently
infected (infected but not yet themselves
infectious); and active infectious cases.
A detailed model incorporates additional refinements: only a certain fraction of
cases are assumed to be infectious, an
infection may be spontaneously cured
and a recovered individual may relapse
and re-develop TB. The outcome is
expressed in terms of a quantity, Ro,
that is called the basic reproductive
number for Mycobacterium tuberculosis,
the causative agent.
Ro represents the -average number of
secondary infectious cases produced
when a single infectious person is introduced into a susceptible population.
When Ro is less than 11, the infection is
unable to sustain itself;
when Ro exceeds 1, an epidemic results. The question is, under what circumstances is either of
these outcomes realised?
Firstly, a minimum
population size is needed
for the transmission to
spread. Secondly, it is relevant to examine what the
consequences are whe ;n Ro
is greater than 1. Based on
an analysis of major TB
epidemics, the researchers
estimated that Ro's range
of probable values could
be anything between 0.74 and 18.58.
The median value was 4.47.
This means that Ro was estimated to
be less than 4.47 in half the number of
recorded epidemics and greater than
4.47 in the other half Interestingly, even
when Ro exceeds 1, aAd an epidemic
results, the following prediction can follow: when conditions remain constant,
the epidemic undergoes an 'aging'
process; it flares up first and then
declines until it attains a stable endemic
level. On an average, an epidemic can be
expected spontaneously to die down -
though not die out - in about
100 years. Therefore, the
authors conclude, "...part of
the observed dramatic decline
Of TB in developed countries
may simply reflect the natural
behaviour of an epidemic ......".
Close examination of the
model reveals that an epidemic
flares up and then subsides to
endemicity on account of the
gradual development, over several generations, of a large pool
of latently infected, and therefore non-infectious, indi-
viduals. Over their lifetimes,
such individuals gradually
become infectious themselves.
Therefore, the majority of
new cases during the mature
stage of an epidemic are on
account of the latently infected
pool, not on account of fresh
infections.
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